药理学参数在晚期非小细胞肺癌紫杉醇化疗指导方案中的运用-东南大学学报医学版

药理学参数在晚期非小细胞肺癌紫杉醇化疗指导方案中的运用

单位：江苏省肿瘤医院, 江苏省肿瘤防治研究所, 南京医科大学附属肿瘤医院肿瘤内科, 江苏南京 210000

分类号：R734.2;R730.53

出版年·卷·期（页码）：2017·36·第五期（681-685）

摘要：

目的：通过随机对照研究中国非小细胞肺癌患者接受紫杉醇治疗后在药理学参数上的个体差异，评估紫杉醇药理学参数与毒性及疗效的相关性，并根据药理学参数进行剂量调节。方法：59例非小细胞肺癌患者采用含紫杉醇的药物治疗方案。紫杉醇的起始剂量为135~175mg·m^-2，患者随机分为实验组29例和对照组30例，从第2周期开始对照组仍旧按照体表面积给药，实验组根据紫杉醇T_C>0.05值进行相应的剂量调整给药。观察两组患者的骨髓细胞学毒性发生率和缓解率。结果：紫杉醇药理参数T_C>0.05在第1周期的个体差异很大，平均值为35 h （范围为22~55 h，CV=25.57%）。17%的患者T_C>0.05在治疗窗（26~31 h）内，75%的患者T_C>0.05大于治疗窗，8%的患者低于治疗窗。采用药理学参数指导用药方式后，总用药量下降了15%。在整个化疗周期内Ⅲ~Ⅳ级毒性，对照组发生率（77%）高于实验组（42%），差异具有统计学意义（P=0.002）。17例患者完成了6个周期的化疗，严重毒性发生率实验组为40%，对照组为65%，两组之间差异具有统计学意义（P=0.031）。紫杉醇剂量的降低对缓解率没有负面影响（实验组为37.93%，对照组为36.67%，P=0.710）。结论：紫杉醇T_C>0.05是紫杉醇药物暴露的关键药理学参数，并且是严重中性粒细胞减少症的预测因子，按照药理学参数来优化患者的用药剂量能够提高紫杉醇用药的安全性和有效性。

Objective:This paper randomized controlled research Chinese patients with non-small cell lung cancer(NSCLC) pharmacokinetic(PK) parameter individual difference who has received paclitaxel(PTX) chemotherapy, and evaluate the correlation between pharmacokinetic parameter paclitaxel and toxicity and efficacy, then adjust the dosage according to the pharmacological parameter. Methods:59 NSCLC patients receiving first-line paclitaxel chemotherapy had been enrolled. 59 Patients were randomized to receive paclitaxel at a starting dose of 135~175 mg·m^-2. 59 patients with NSCLC were randomly divided into experimental group and control group, 29 cases in experimental group, 30 cases in control group. Starting from the second cycle, PTX dose based on body surface area (BSA) in control group and in experimental group PTX dose based on PK. Severe toxicities of bone marrow and response rates were compared by experimental group and control group. Results:Exposure values from 1st cycle showed great PTX PK variability, with a mean T_{C > 0.05} of 35 h (range=22-55 h, CV=25.57%). 17% of these patients had PTX exposure values within the target range (26 to 31 h), while 75% were above target exposure, and 8% patients showed PTX exposure below target. Exposure optimization of PTX in experimental group led to an overall 15% dose reduction. In 17 patients with 6 cycles of chemotherapy completed, severe neutropenia rate in experimental group at cycle 6 was 40% compared to 65% in control group(P=0.031). Response rate was also evaluated and showed no negative impact (37.93% in experimental group vs 36.67% in control group,P=0.710). A higher neuropathy rate was observed in control group (77%) compared to experimental group (42%)(P=0.002). Conclusion:The time above a PTX plasma concentration of 0.05μmol·L^-1(T_C>0.05) is the key PK parameter to measure systemic exposure to the drug and is a predictor of severe neutropenia. According to the parameter of PTX pharmacology with exposure optimized PTX dose can improve the effectiveness and safety of PTX chemotherapy.

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